scholarly journals Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD-1.3A genotype in patients with systemic lupus erythematosus

2010 ◽  
Vol 62 (6) ◽  
pp. 1702-1711 ◽  
Author(s):  
Helga Kristjansdottir ◽  
Kristjan Steinsson ◽  
Iva Gunnarsson ◽  
Gerdur Gröndal ◽  
Kristjan Erlendsson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Lower Expression

The Systemic Activation of Programmed Death 1-PD-L1 Axis Protects Systemic Lupus Erythematosus Model from Nephritis

2017 ◽  
Vol 46 (5) ◽  
pp. 371-379 ◽  
Author(s):  
Wenjun Liao ◽  
Hua Zheng ◽  
Sha Wu ◽  
Yanmei Zhang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Activated T Cells ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Ifn Γ

Background: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. Methods: The murine PD-L1-Ig was injected into SLE-prone mice. The proteinuria and survival ratio were monitored. The production of anti-dsDNA autoantibodies and cytokines in serum were measured by enzyme-linked immunosorbent assay. The cytokine-producing T cells (interferon-γ, IFN-γ and IL-17α) in kidney and spleen were detected with flowcytometry. The pathological evaluation of the Ig deposition in the glomeruliand was determined with immunofluorescence. Lymphocytes in 24-h urine were detected with flowcytometry. Results: The systemic administration of PD-L1-Ig activated PD-1-PD-L1 axis of CD4+ T lymphocytes, suppressed Th17 formation in many organs, including the spleen and the kidney, demolished abnormal production of cytokines (IFN-γ, IL-17, and IL-10) and anti-dsDNA autoantibodies in serum, inhibited immunoglobulin G deposition in the glomeruli with the decrease of proteinuria, and activated T cells in urine. Accordingly, the systemic conjugation of PD-L1-PD-1 impaired renal autoimmune injure and prolonged survival time. Conclusion: Our research demonstrated that the protective function of systemic activation of PD-1-PD-L1 axis with PD-L1-Ig attenuates the nephritis in SLE-prone mice, which facilitates us to understand the suppressive function of PD-1-PD-L1 axis in the pathogenesis and progress of the lupus nephritis, and to explore a possible effective therapeutic strategy to SLE.

scholarly journals The decreased expression of IKBKE in systemic lupus erythematosus

2020 ◽  
Vol 39 (9) ◽  
pp. 2611-2617
Author(s):  
Tingting Zhu ◽  
Jiaqi Hong ◽  
Zongwen Shuai ◽  
Shengqian Xu ◽  
Danfeng Qian ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Regulatory Function ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Lower Expression ◽  
Mrna Expression Levels

Abstract Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.

scholarly journals Programmed death 1 (PD-1) serum level and gene expression in recent onset systemic lupus erythematosus patients

2021 ◽  
Vol 43 (3) ◽  
pp. 213-218
Author(s):  
Sherine A. Bassiouni ◽  
Hanaa M. Abdeen ◽  
Heba K. Morsi ◽  
Maysaa E. Zaki ◽  
Maha Abdelsalam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Serum Level ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Recent Onset ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Onset Systemic Lupus Erythematosus
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